Prognostic significance and mechanism of Treg infiltration in human brain tumors.

Regulatory T cells (Tregs) accumulate in tumors and can contribute to the dismal immune responses observed in these tumors. We reported that the percentage of tumor infiltrating Tregs is strongly correlated with the WHO grade of the brain tumor. We now report on the clinical follow-up of this patient cohort (n=83). Subgroup analyses in patients with glioblastomas (n=29) showed a moderate, not significant, inverted association between Tregs and survival. We further show that Tregs in glioblastomas, in contrast to other tumor infiltrating effector lymphocytes, highly express the CCR4 chemokine receptor. Moreover, the CCR4 ligand CCL22 is secreted by glioblastomas and may explain the specific Treg accumulation seen in these tumors.